STABILIZING EXCIPIENTS FOR THERAPEUTIC PROTEIN FORMULATIONS
The invention encompasses therapeutic formulations comprising a protein active ingredient and a stabilizing excipient, methods of improving stability in a therapeutic formulation comprising a protein active ingredient by adding a stability-improving amount of a stabilizing excipient to the therapeutic formulation, and methods of reducing adverse infusion-related effects in a patient, comprising administering to a patient in need thereof a therapeutic formulation comprising a protein active ingredient and a stabilizing excipient.
1 . A therapeutic formulation comprising a protein active ingredient and a stabilizing excipient.
2 . (canceled)
3 . (canceled)
4 . The formulation of claim 1 , wherein the formulation contains at least about 1 mg/mL of protein active ingredient.
5 . (canceled)
6 . The formulation of claim 4 , wherein the formulation contains at least 100 mg/mL of protein active ingredient.
7 . (canceled)
8 . (canceled)
9 . The formulation of claim 1 , wherein the protein active ingredient is selected from the group consisting of an antibody, an antibody-drug conjugate, an enzyme, a cytokine, a neurotoxin, a fusion protein, an immunogenic protein, a PEGylated protein, and an antibody fragment.
10 . The formulation of claim 1 , wherein the formulation contains at least about 1 to about 5000 ppm of the stabilizing excipient.
11 . (canceled)
12 . (canceled)
13 . The formulation of claim 1 , wherein the stabilizing excipient excludes polypropylene block copolymers.
14 . The formulation of claim 1 , wherein the stabilizing excipient is selected from the group consisting of polypropylene glycol, adducts of polypropylene glycol, and random copolymers comprising propylene oxide units.
15 . The formulation of claim 14 , wherein the stabilizing excipient is a polypropylene glycol homopolymer.
16 . The formulation of claim 15 , wherein the polypropylene glycol homopolymer has a number-average molecular weight between about 300 and 5000 Daltons.
17 . The formulation of claim 16 , wherein the polypropylene glycol homopolymer has a number-average molecular weight of about 425 Daltons.
18 . The formulation of claim 16 , wherein the polypropylene glycol homopolymer has a number-average molecular weight of about 1000 Daltons.
19 . (canceled)
20 . The formulation of claim 15 , wherein the polypropylene glycol homopolymer is a linear polymer with at least two hydroxyl groups.
21 . The formulation of claim 20 , wherein the linear polymer contains two or three hydroxyl groups.
22 . The formulation of claim 14 , wherein the polypropylene glycol is a branched polymer.
23 . (canceled)
24 . (canceled)
25 . The formulation of claim 14 , wherein the stabilizing excipient is an adduct of polypropylene glycol.
26 . (canceled)
27 . The formulation of claim 1 , wherein the stabilizing excipient is a hydrophobically modified cellulosic polymer.
28 . The formulation of claim 27 , wherein the hydrophobically modified cellulosic polymer is selected from the group consisting of a methylcellulose, a hydroxypropyl methylcellulose, a hydroxypropyl cellulose, and a hydroxyethyl cellulose.
29 . The formulation of claim 28 , wherein the hydrophobically modified cellulosic polymer is not a sodium carboxymethyl cellulose.
30 - 41 . (canceled)
42 . The formulation of claim 1 , wherein the formulation further comprises a second stabilizing excipient.
43 . The formulation of claim 1 , wherein the formulation excludes conventional surfactants.
44 - 49 . (canceled)
50 . A method of improving stability in a therapeutic formulation comprising a protein active ingredient by adding a stability-improving amount of a stabilizing excipient to the therapeutic formulation.
51 - 54 . (canceled)
55 . A method of reducing adverse infusion-related effects in a patient, comprising administering to a patient in need thereof a therapeutic formulation comprising a protein active ingredient and a stabilizing excipient, wherein infusing the therapeutic formulation into the patient results in fewer adverse infusion-related effects than infusing a control formulation into the patient, wherein the control formulation lacks the stabilizing excipient.
56 . (canceled)